共查询到20条相似文献,搜索用时 78 毫秒
1.
G Pezzoli S Tesei C Ferrante E Cossutta A Zecchinelli G Scarlato 《Movement disorders》1988,3(1):37-45
In an open-label study, we substituted conventional levodopa plus benserazide: 100/25 (Madopar) with a controlled-release form (HBS) in 18 fluctuating parkinsonian patients for 24 months. Significantly positive results were obtained in both peak-dose and diphasic dyskinesias up to 12 months of treatment; morning akinesias were also improved up to 6 months. A general trend of deterioration, compared to the first 3-6 months of HBS treatment, was observed in "off" fluctuations after 1 year: akinesias due to a delayed response worsened after 1 year of treatment also when compared with the conventional treatment. Positive results were obtained with new HBS on standard Madopar-related psychiatric disorders. 相似文献
2.
Caraceni T. Nordera N. Lamperti E. Lorizio A. 《The Italian Journal of Neurological Sciences》1989,10(4):407-414
The most important current problem in the treatment of Parkinson disease in the so-called L-dopa long-term-treatment syndrome.
We present here the results of our experience with Madopar HBS in the treatment of two groups of patients suffering from L-dopa
long-term treatment syndrome. In the first study we replaced the standard Madopar with Madopar HBS. In the second study, after
identifying the most disabling “off” periods, we added Madopar HBS to the previous treatment in such a way as to control these
“off” phases.
Our study suggests that Madopar HBS is useful in reducing typical fluctuation phenomena in the majority of patients.
Sommario Attualmente il problema più importante nel trattamento del morbo di Parkinson è costituito dalla cosiddetta “sindrome da trattamento cronico con L-dopa”. Presentiamo qui di seguito i risultati della nostra esperienza con Madopar HBS nel trattamento di 2 gruppi di pazienti affetti da tale sindrome. Nella prima parte dello studio abbiamo sostituito del tutto il Madopar standard con Madopar HBS, nella seconda parte, dopo aver identificato il periodo “off” maggiormente invalidante, abbiamo aggiunto Madopar HBS al trattamento precedente in modo che fosse efficace sulla fase off così identificata. Il nostro lavoro suggerisce che il Madopar HBS è utile nel ridurre le fluttuazioni motorie nella maggioranza dei pazienti parkinsoniani.相似文献
3.
E. Dupont A. Andersen J. Boas E. Boisen R. Borgmann A. C. Helgetveit M. O. Kjær T. N. Kristensen B. Mikkelseng H. Pakkenberg J. Presthus R. Stien J. Worm-Petersen D. Buch 《Acta neurologica Scandinavica》1996,93(1):14-20
In this Danish-Norwegian randomized double-blind parallel-group multicentre study, we compared the therapeutic response of slow-release Madopar HBS® to standard Madopar® in 134 de novo patients with idiopathic Parkinson's disease during a 5-year period. The drugs were dosed according to the individual need of the patients. The Webster, NUDS, UPDRS and Hoehn & Yahr scales were used for evaluation of symptoms. Addition of a morning dose of standard Madopar 62.5 mg was allowed after 6 months. Bromocriptine could be administered but not Selegiline. Sixty-five patients got Madopar HBS and 69 standard Madopar. Surprisingly, no differences were found as to the mean daily levodopa dose, the mean number of daily doses or the use of and doses of bromocriptine. Unexpectedly, we found a trend towards a more frequent use of a morning dose of standard Madopar in the group treated with the standard formulation. No differences were observed in the occurrence of motor fluctuations or dyskinesia, the incidence of which was relatively low. Sustained-release Madopar (HBS) thus proved to be as effective as standard Madopar in the long-term treatment of de novo parkinsonian patients, but the drug showed no advantage in postponing or reducing the long-term levodopa treatment problems. 相似文献
4.
Summary 20 patients with Parkinson's disease and a fluctuating response to chronic treatment with conventional L-dopa preparations participated in an open randomized trial comparing two sustained-release L-dopa preparations (Madopar HBS, Sinemet CR4). While a majority (15 patients, 7 on Madopar HBS and 8 on Sinemet CR4) showed a favourable response after 2 months of slow-release L-dopa treatment the clinical benefit remained stable in only 2 patients on Madopar HBS and 3 patients on Sinemet CR4 over the entire follow-up period of 12 months. Reasons for treatment failure were increased peak-dose or biphasic dyskinesias or prolonged off-periods. This preliminary study failed to demonstrate clinically significant advantages of one slow-release principle over the other. 相似文献
5.
Madopar Hydrodynamically Balanced System (HBS), a new sustained-release levodopa preparation, was used to control severe nightly disabilities in 15 outpatients suffering from Parkinson's disease in an advanced state and with long-term levodopa therapy. This medication was given ante noctem in addition to an otherwise unchanged daily regimen of levodopa administration. In 13 patients a considerable diminution in nocturnal akinesia and in the frequency of waking up was reached with a mean dosage of 308 mg of Madopar HBS. Early morning akinesia was only slightly alleviated in four patients. The nocturnal off-period pain disappeared in one patient. Adverse effects consisted of nocturnal dyskinesia in two patients and early morning dystonia in another two patients. The regular use of sleeping pills was clearly reduced after Madopar HBS therapy. 相似文献
6.
Summary In five levodopa (l-dopa)-treated patients with Parkinson's disease with severe fluctuations of motor performance, plasma l-dopa as well as dopamine levels were measured during 2 days, first under optimal standard l-dopa with peripheral decarboxylase inhibitor (PDI) and then after a dose adjustment period using slow-release l-dopa/benserazide (Madopar HBS) in an open inpatient trial. Three patients benefited from the slow-release preparation; two patients deteriorated with a tendency to have an unpredictable response, a delay to turn on with the first dose in the morning, as well as an increase in dyskinesia corresponding to l-dopa cumulation during the day. These problems were subsequently also seen during the follow-up period of 1 year in those patients who benefited from Madopar HBS as inpatients. This might indicate that patient compliance is more difficult with the new formulation. After 1 year all patients had returned to their previous standard l-dopa/PDI treatment. l-Dopa levels continued to fluctuate, but to a lesser degree with Madopar HBS. The equivalent l-dopa dosage had to be increased by 56% (29–100%) with Madopar HBS while mean dopamine levels increased in four patients (by 47–257%) without the occurrence of peripheral side-effects. This implies that with the new formulation more l-dopa is metabolized to dopamine and explains the necessity to increase the equivalent l-dopa dosage. 相似文献
7.
N. O. Jensen E. Dupont E. Hansen B. Mikkelsen B. O. Mikkelsen 《Acta neurologica Scandinavica》1988,77(5):422-425
Flucuations in motor performance is a major problem in long-term levodopa treatment of Parkinsonian patients. A slow release preparation of levodopa with benserazide, Madopar HBS, has been developed in an attempt to decrease this problem. Eleven of 22 Parkinsonian patients with advanced disease and marked fluctuations experienced long-lasting benefit with reduction of their fluctuations in motor performance on treatment with Madopar HBS; 11 dropped out within the first 5 months of the trial. This was probably due to lack of experience with the effect of this new slow-release formulation. Nine patients (82%) required an additional dose of standard Madopar, especially in the morning. Significant improvements were found for akinetic phenomenon and dystonic cramps, and with the global evaluation of motor fluctuations. The occurrence of peak dose dyskinesia remained unchanged. No abnormalities in laboratory values were found. 相似文献
8.
Fourteen patients with Parkinson's disease and motor fluctuations were given 125 mg of Madopar HBS or placebo twice a day in addition to their optimal standard Madopar treatment in a double-blind, cross-over study. Clinical response was evaluated by the King's College Hospital Parkinson's Disease Rating Scale, the Mobility in Bed Scale and self-scoring diaries. A significant improvement with the drug was found according to the rating scales, whereas evaluation by self-scoring diaries showed no significant changes. In three patients we observed worsening of abnormal involuntary movements. The present trial suggests that a low dose of Madopar HBS can be useful in addition to levodopa therapy in some patients on long-term treatment. 相似文献
9.
The efficacy of a novel oral sustained-release preparation of levodopa/benserazide (Madopar HBS) was compared to that of previous conventional levodopa/benserazide treatment in 15 patients with idiopathic Parkinson's disease and with severe fluctuations in motor response to long-term levodopa therapy. In ten patients who suffered from clear-cut "end-of-dose" deterioration, significant benefit was obtained on HBS form, while 5 patients did not respond well to the new levodopa preparation. Plasma levels of levodopa were more stable with HBS compared to conventional levodopa preparation in our patients, although doses of HBS form required for an optimal response averaged 1.48 times that of previous conventional levodopa. 相似文献
10.
The objective was to assess the single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following administration of a new dual-release and conventional slow-release formulation of levodopa/benserazide in the dose ratio of 4:1. In an open-label, two-way cross-over study, 20 healthy volunteers were randomized to receive first either Madopar DR or Madopar HBS for 8 days. Then they crossed over to the other formulation. A first dose of 200 mg levodopa and 50 mg benserazide ('250' mg) was given on day 1, '125' mg t.i.d. on the subsequent 6 days (days 2-7), followed by '250' mg on day 8. The two treatment periods of 8 days were separated by a wash-out period of at least 7 days. Blood samples were taken at specific times over a 12-hour period (day 1) or a 36-hour period (day 8). Plasma concentrations of levodopa and 3-O-methyldopa were measured by high-performance liquid chromatography for pharmacokinetic evaluation. The pharmacokinetics of levodopa after a single-dose administration (day 1) of Madopar DR and Madopar HBS were significantly different as reflected by the respective mean values of maximum plasma concentration (C(max) 1.99 vs. 0.82 mg x l-1), time to reach maximum concentration (t(max) 0.7 vs. 2.6 h) and area under the plasma concentration-time curve (AUC(0- infinity ) 4.52 vs. 3.18 mg x h x l-1). The respective values after multiple doses (day 8) were: C(max) 1.98 vs. 0.93 mg x l-1, t(max) 0.7 vs. 2.3 h and AUC(0-infinity ) 4.84 vs. 3.96 mg x h x l-1. The relative bioavailability (Madopar DR vs. Madopar HBS) was 1.73 on day 1 and 1.32 on day 8. Bioequivalence could not be demonstrated for log-transformed data of AUC and C(max) within a predefined range of 80-125 and 70-143%, respectively. In conclusion, the observed differences in C(max), t(max) and AUC are consistent with a faster rate and higher extent of levodopa absorption after administration of Madopar DR. Statistical evaluation of these kinetic data showed that Madopar DR is not bioequivalent to Madopar HBS. 相似文献
11.
A comparison of the effects of controlled-release levodopa (Madopar CR) with conventional levodopa in late Parkinson''s disease.
下载免费PDF全文
![点击此处可从《Journal of neurology, neurosurgery, and psychiatry》网站下载免费的PDF全文](/ch/ext_images/free.gif)
D G MacMahon D Sachdev H G Boddie C J Ellis B R Kendal N A Blackburn 《Journal of neurology, neurosurgery, and psychiatry》1990,53(3):220-223
In this multicentre study a controlled-release formulation of levodopa and the decarboxylase inhibitor benserazide (Madopar CR) was evaluated in patients with Parkinson's disease exhibiting dose-related fluctuations in motor performance in response to conventional levodopa preparations. The effect of Madopar CR, with or without conventional levodopa/benserazide, on the proportion of time spent "on", "off" or "intermediate" was compared with that of previous conventional levodopa/decarboxylase inhibitor therapy. Evaluation of the two periods of optimum therapy was based on both patient diary data and investigator opinion. Forty seven patients completed the study but full patient diaries were available for only 37. The mean optimum total daily dosage of conventional Madopar was 820 mg taken in a mean of 6.4 doses, compared with a mean optimum daily dosage of combined Madopar CR and conventional Madopar of 1088 mg, taken in a mean of 5.2 doses. Conventional Madopar was taken in addition to Madopar CR in all but eight patients. Madopar CR was felt to be advantageous in 83% and disadvantageous in 11% of patients completing the study. Considering the 37 patients for whom diary data were available, Madopar CR therapy resulted in an increase in the mean time spent "on" (p = 0.016) and a decrease in the mean time spent "off" (p = 0.029) compared with conventional Madopar alone. Individually 25 out of 37 had an increase in "on" time and 19 out of 37 experienced a decrease in "off" time. Thus Madopar CR was found to be beneficial in a significant proportion of patients experiencing fluctuations in response to conventional levodopa. 相似文献
12.
A Martinez-Campos P Giovannini E Parati A Novelli T Caraceni EE Müller 《Journal of neurology, neurosurgery, and psychiatry》1981,44(12):1116-1123
Madopar, a combination of levodopa with benserazide, induced an inconsistent rise in plasma growth hormone in unmedicated patients with Parkinson's disease and in controls, and a greater growth hormone rise in Parkinsonian subjects on chronic Madopar therapy. In subjects on chronic therapy with levodopa and carbidopa (Sinemet), the growth hormone releasing effect of Madopar was blunted. Madopar increased plasma prolactin (PRL) in controls, unmedicated patients and patients on Madopar therapy while in patients on Sinemet therapy the PRL-releasing effect of Madopar was strikingly reduced. Since these data were interpreted as due to a defective dopamine tone in the hypothalamus of Parkinsonian subjects on Madopar but not Sinemet therapy, a direct dopamine receptor agonist, lisuride was administered. Lisuride, however, elicited a blunted growth hormone response both in patients on Madopar and Sinemet therapy, without revealing a state of supersensitivity of dopamine receptors for growth hormone control in Parkinsonian subjects on Madopar therapy. No difference was present in the PRL-lowering effect of lisuride in the different experimental groups. These findings suggest that: (1) hypothalamic dopamine function is impaired in Parkinsonian subjects on Madopar therapy, preserved in unmedicated patients and enhanced in patients on Sinemet therapy; (2) the endocrine effects observed in Parkinsonian subjects on chronic Madopar therapy may be due to some penetration of benserazide across the blood brain barrier in the region of the hypothalamus; (3) since Madopar and Sinemet are in essence equally effective antiparkinsonian remedies, penetration of benserazide does not occur across the blood brain barrier surrounding the nigrostriatal system. 相似文献
13.
目的 评价新型多巴胺受体激动剂普拉克索联合美多巴与单用美多巴治疗帕金森病(PD)患者的疗效及安全性. 方法 采用随机对照开放式研究,将70例PD患者按照随机数字表法分为普拉克索+美多巴组和美多巴组,每组各35例.治疗12周后判断其疗效及安全性.疗效判定的主要指标为统一PD评定量表第Ⅲ部分(UPDRSⅢ)的运动检查总评分相对患者基线的变化和第Ⅱ部分(UPDRS Ⅱ)的日常生活活动能力总评分相对患者基线的变化;次要指标为第Ⅰ部分(UPDRS Ⅰ)的精神、行为和情感总评分相对患者基线的变化和第Ⅳ部分(UPDRS Ⅳ)的治疗并发症总评分相对患者基线的变化和美多巴药物每日剂量相对基线的变化.安全性指标依据药物的不良反应来判定. 结果 普拉克索+美多巴组患者UPDRS Ⅲ总评分均值与基线相比下降了11.40分,高于美多巴组(9.26分),比较差异有统计学意义(P<0.05);UPDRS Ⅱ总评分均值与基线相比下降了4.57分,高于美多巴组(4.50分),比较差异无统计学意义(P<0.05);UPDRS Ⅰ总评分均值与基线相比下降了0.66分,低于美多巴组(1.14分),差异无统计学意义(P0.05);UPDRS Ⅳ总评分均值与基线相比下降了0.22分,美多巴组则升高了0.06分,差异有统计学意义(P<0.05).与基线相比,治疗后12周普拉克索+美多巴组美多巴的日用量下降了163.57 mg/d,美多巴组升高了8.57 mg/d,差异有统计学意义(P<0.05).普拉克索+美多巴组在治疗后12周发生疗效减退、症状波动、异动症的例数均低于美多巴组,差异有统计学意义(P<0.05).美多巴组出现了明显的疗效减退、症状波动、异动症,而普拉克索+美多巴组无明显的上述症状,但有2例出现突然入睡发作、1例嗜睡、1例直立性低血压. 结论 普拉克索+美多巴组在改善PD运动功能方面优于美多巴组,在日常活动,精神、行为和情绪方面疗效相似.同时服用普拉克索可以明显减少美多巴的用量及其治疗后所引起的并发症(疗效减退、症状波动及异动症)的发生率.普拉克索可引起突然入睡发作、嗜睡、直立性低血压等副作用. 相似文献
14.
Ten patients with idiopathic Parkinson's disease and severe motor-fluctuations participated in an open inpatient trial comparing the efficacy of standard L-Dopa/benserazide (Madopar) treatment with that of an oral sustained-release preparation (Madopar HBS) combined with the standard drug. Clinical assessments of the patients' parkinsonian disabilities were performed daily by one of the investigators and subjects kept self-scoring "on-off" diaries throughout the trial. Plasma concentrations of L-Dopa were followed during both types of therapy in five cases using standard high performance liquid chromatography technique. Sustained-release L-Dopa treatment led to a reduction in end-of-dose deterioration and on-off swings in six patients and doses needed averaged 1.6-fold of previous standard L-Dopa. Drug-induced dyskinesias decreased in one case with sustained-release therapy, remained unchanged in three, and increased in six cases when compared with conventional L-Dopa. Plasma levels of L-Dopa were more stable with the sustained-release preparation in four of five patients. During subsequent outpatient follow-ups of up to 4 months, three of the six responders in this study continued to obtain benefit from the trial drug. It is concluded that oral sustained-release L-Dopa treatment can reduce response-fluctuations in patients with Parkinson's disease. 相似文献
15.
In a crossover study we compared the single dose effect of 200 mg levodopa (plus decarboxylase inhibitor) in the form of Madopar with that of Madopar Dispersible on the motor performance of eight patients with Parkinson’s disease, after 12 h without their ordinary anti-parkinsonian medication and food intake. Objective recording of their performance was done with an opto-electronic camera and automatic computerised treatment of the movement data and with scoring according to the United Parkinson’s Disease Rating Scale. We conclude that Madopar Dispersible has a much faster and more constant onset of action than the standard preparation (25 vs 46 min.). The effect duration and the effects on motor performance were otherwise the same. 相似文献
16.
The clinical efficacy of single morning doses of levodopa methyl ester: dispersible Madopar and Sinemet plus in Parkinson disease. 总被引:1,自引:0,他引:1
M J Steiger F Stocchi L Bramante S Ruggieri N P Quinn 《Clinical neuropharmacology》1992,15(6):501-504
For many patients with Parkinson disease and levodopa-related motor fluctuations, the latency to onset of action of a single dose of a levodopa preparation may be both long and variable. In an effort to find a more rapidly acting and reliable preparation of levodopa, we therefore studied the efficacy of single doses of an oral solution of 250 mg of levodopa methyl ester (ME) with benserazide, 50 mg and of a molar equivalent dose of dispersible Madopar (DM) (50/200) in 13 patients in the fasting state after overnight drug withdrawal. The response of seven of these patients was compared to that after two Sinemet 25/100. The latency to "on" was equally fast with ME and DM, and significantly faster than after standard Sinemet. The duration of "on" was similar with all three. Because of this more rapid relief of "off" periods, both ME and DM offer a potential clinical advantage over standard preparations of levodopa. 相似文献
17.
Enantiomeric composition of urinary salsolinol in Parkinsonian patients after Madopar 总被引:2,自引:0,他引:2
P. Dostert M. Strolin Benedetti G. Dordain D. Vernay 《Journal of neural transmission (Vienna, Austria : 1996)》1989,1(4):269-278
Summary Urinary salsolinol output had been shown to be lower in Parkinsonian patients than in controls and to increase largely after L-dopa therapy. It had also been established that the R enantiomer of salsolinol is either the predominant or the sole enantiomer present in the urine of healthy subjects.When Madopar was administered to Parkinsonians, the enantiomeric composition of urinary salsolinol showed an S/R ratio around 1. Considering brain and plasma concentrations in dopamine, acetaldehyde and pyruvate, it is suggested that, under physiological conditions, urinary salsolinol should have a central origin in humans. Conversely, urinary salsolinol in Madopar-treated Parkinsonian patients might be predominantly formed at the periphery. 相似文献
18.
Increased life expectancy resulting from addition of l-deprenyl to Madopar® treatment in Parkinson's disease: A longterm study 总被引:5,自引:0,他引:5
W. Birkmayer J. Knoll P. Riederer M. B. H. Youdim Vera Hars J. Marton 《Journal of neural transmission (Vienna, Austria : 1996)》1985,64(2):113-127
Summary In an open, uncontrolled study the longterm (9 years) effect of treatment with Madopar® alone (n=377) or in combination with l-deprenyl (selegiline, selective monoamine oxidase type B inhibitor) (n=564) have been compared in Parkinsonian patients. In patients who lost their response to conventional Madopar therapy the addition of l-deprenyl resulted in a significant recouping of levodopa effect. The survival analysis revealed a significant increase of life expectancy in Madopar-l-deprenyl group regardless of the fact whether or not the significant demographic differences between the two groups were taken into account. Although the mechanism underlying this action of l-deprenyl is not known, the results are interpreted as indicating l-deprenyl's ability to prevent or retard the degeneration of striatal dopaminergic neurons. l-Deprenyl is the first anti-Parkinson drug having such a property. This hypothesis is not far fetched since l-deprenyl selectively prevents the degeneration of striatal dopaminergic neurons induced in animals by the illicit drug l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Since latter compound is known to cause Parkinsonism in man and primates or Parkinson-like neurochemical and pathological changes in other animals the implications of the present study involving monoamine oxidase activity and l-deprenyl are apparent. 相似文献
19.
T A Caraceni I Celano E Parati F Girotti 《Journal of neurology, neurosurgery, and psychiatry》1977,40(12):1142-1146
Twenty-six patients affected by Parkinson's disease were treated with a 2-Br-alpha-ergocriptine (CB 154): 14 cases were given CB 154 alone, and 12 were given CB 154 along with L-dopa plus benserazide (Madopar). Both CB 154 and combined therapy (CB 154+Madopar) induced a significant improvement in total disability score, tremor, rigidity, akinesia, self-sufficiency, and some motor performance tests (dynamic tests). No significant difference was found between results obtained with CB 154 therapy and with Madopar treatment, while the improvement induced by combined therapy (CB 154+Madopar) was significantly higher than that obtained by Madopar alone. The averse reactions caused by CB 154 alone or associated with Madopar are similar to those observed during other dopaminergic treatment. CB 154 alone or combined with Madopar appears to be a useful advance in the management of Parkinson's disease. 相似文献
20.
Stocchi F Fabbri L Vecsei L Krygowska-Wajs A Monici Preti PA Ruggieri SA 《Clinical neuropharmacology》2007,30(1):18-24
A possible cause of motor fluctuations in patients with Parkinson disease is the erratic drug absorption. In a randomized double-blind double-dummy study of melevodopa (levodopa methyl ester), a highly soluble levodopa pro-drug plus carbidopa (CHF 1512) was compared to a standard formulation of levodopa/carbidopa (LD/CD) in 74 fluctuating Parkinson disease patients. The first afternoon, LD/CD tablet was substituted with an equimolar dose of CHF 1512. The study lasted 4 weeks and was followed by an 8-week (optional) open phase. The primary efficacy variable was latency to "on." Patients randomized to receive CHF 1512 had a significative shorter latency to "on" than those randomized to LD/CD and a similar "on" duration. The safety profile of CHF 1512 was also comparable with LD/CD. 相似文献